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Strain Name:
B6J.Cg-Atp1a1tm2Ling/Mmnc
Stock Number:
069685-UNC
Citation ID:
RRID:MMRRC_069685-UNC
Other Names:
C57B/6J

Strain Information

Atp1a1tm2Ling
Name: ATPase, Na+/K+ transporting, alpha 1 polypeptide; targeted mutation 2, Jerry B Lingrel
Synonyms: alpha1S
Type: Allele
Species: Mus musculus
Chromosome: 3
Alteration at locus: Knock-In
Atp1a1
Name: ATPase, Na+/K+ transporting, alpha 1 polypeptide
Synonyms: Atpa-1
Type: Gene
Species: Mouse
Chromosome: 3
Alteration at locus: Knock-In
NCBI: 11928
HGNC: HGNC:799
Homologene: 564
Genetic Alterations
Mutations in the mouse Atp1a1 gene convert its ouabain binding site (also known as: cardiac glycoside or cardiotonic steroid receptor) from low to high affinity ouabain binding (α1S, ouabain Sensitive)
Genotype Determination
  • Genotyping Protocol(s)
  • Center protocol and contact for technical support will be shipped with mice.
  • ES Cell Line
    Duffy derived from 129S6/SvEvTac
    Phenotype
    Amino acid changes on the alpha 1 subunit isoform of Na,K-ATPase render these mice sensitive to ouabain binding. The result is a "humanized" mouse with respect to ouabain binding and ouabain actions on cardiovascular, kidney, brain, and other functions. In humans, both alpha 1 and alpha2 isoforms bind ouabain with nanomolar sensitivity; whereas in WT mice, only the alpha 2 isoform binds ouabain with high sensitivity.
    MeSH Terms
    • Animals
    • Base Sequence
    • Drug Resistance
    • Enzyme Inhibitors/pharmacology
    • Hemodynamics
    • Immunosorbent Techniques
    • Mice
    • Mice, Knockout
    • Molecular Sequence Data
    • Muscle, Skeletal/enzymology
    • Mutagenesis, Site-Directed
    • Myocardial Contraction/physiology
    • Myocardium/enzymology
    • Ouabain/metabolism
    • Ouabain/pharmacology
    • Receptors, Adrenergic, beta/physiology
    • Sodium-Calcium Exchanger/analysis
    • Sodium-Calcium Exchanger/physiology
    • Sodium-Potassium-Exchanging ATPase/deficiency
    • Sodium-Potassium-Exchanging ATPase/genetics
    • Sodium-Potassium-Exchanging ATPase/physiology
    • Transfection
    • Tritium
    • Cell Line
    • Cells, Cultured
    • Cyclic AMP-Dependent Protein Kinases/metabolism
    • Enzyme Activation/drug effects
    • Female
    • Fluorescence Resonance Energy Transfer
    • Humans
    • Immunoprecipitation
    • Ion Transport/drug effects
    • Isoenzymes/genetics
    • Isoenzymes/metabolism
    • Isoproterenol/pharmacology
    • Kinetics
    • Luminescent Proteins/genetics
    • Luminescent Proteins/metabolism
    • Male
    • Membrane Proteins/genetics
    • Membrane Proteins/metabolism
    • Myocytes, Cardiac/cytology
    • Myocytes, Cardiac/drug effects
    • Myocytes, Cardiac/metabolism
    • Phorbol 12,13-Dibutyrate/pharmacology
    • Phosphoproteins/genetics
    • Phosphoproteins/metabolism
    • Phosphorylation
    • Protein Kinase C/metabolism
    • Sodium/metabolism
    • Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors
    • Sodium-Potassium-Exchanging ATPase/metabolism
    • Calcium Signaling/drug effects
    • Dose-Response Relationship, Drug
    • Isoenzymes
    • Membrane Potentials
    • Mice, Transgenic
    • Mutation
    • Myocytes, Cardiac/enzymology
    • Sarcoplasmic Reticulum/drug effects
    • Sarcoplasmic Reticulum/enzymology
    • Sodium-Calcium Exchanger/metabolism
    • Binding Sites
    • Biological Evolution
    • Cardiac Glycosides/metabolism
    • Ligands
    • Receptors, Steroid/drug effects
    • Receptors, Steroid/physiology
    • Binding Sites/physiology
    • Mice, Mutant Strains
    • Natriuresis/drug effects
    • Natriuresis/physiology
    • Protein Isoforms/physiology
    • Water-Electrolyte Balance/drug effects
    • Water-Electrolyte Balance/physiology
    • Adrenocorticotropic Hormone/pharmacology
    • Blood Pressure
    • Conserved Sequence
    • Genetic Engineering
    • Hypertension/chemically induced
    • Hypertension/enzymology
    • Protein Isoforms
    • Sodium-Potassium-Exchanging ATPase/chemistry
    Strain Development

    A targeting vector designed to alter several amino acids impacting ouabain binding was transfected into Duffy embryonic stem (ES) cells (derived from 129S6). Correctly targeted ES cells were injected into blastocysts. Chimeric offspring were bred to Black Swiss mice for two generations. The mice were further backcrossed to B6 mice for and extended period of time.


    Suggested Control Mice
    C57B/6J
    MMRRC Genetic QC Summary
    The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@med.unc.edu. Older strains may not have this information.
    • Cancer
    • Cardiovascular
    • Cell Biology
    • Models for Human Disease
    • Neurobiology
    Donor
    Jerry Lingrel, Ph.D., UNIV OF CINCINNATI.
    Primary Reference

    Dostanic I, Schultz Jel J, Lorenz JN, Lingrel JB. The alpha 1 isoform of Na,K-ATPase regulates cardiac contractility and functionally interacts and co-localizes with the Na/Ca exchanger in heart. J Biol Chem. 2004 Dec 24;279(52):54053-61. doi: 10.1074/jbc.M410737200. Epub 2004 Oct 14. (Medline PMID: 15485817)

    Bossuyt J, Despa S, Han F, Hou Z, Robia SL, Lingrel JB, Bers DM. Isoform specificity of the Na/K-ATPase association and regulation by phospholemman. J Biol Chem. 2009 Sep 25;284(39):26749-57. doi: 10.1074/jbc.M109.047357. Epub 2009 Jul 28. (Medline PMID: 19638348)

    Despa S, Lingrel JB, Bers DM. Na(+)/K)+)-ATPase α2-isoform preferentially modulates Ca2(+) transients and sarcoplasmic reticulum Ca2(+) release in cardiac myocytes. Cardiovasc Res. 2012 Sep 1;95(4):480-6. doi: 10.1093/cvr/cvs213. Epub 2012 Jun 27. (Medline PMID: 22739122)

    Lingrel JB. The physiological significance of the cardiotonic steroid/ouabain-binding site of the Na,K-ATPase. Annu Rev Physiol. 2010;72:395-412. doi: 10.1146/annurev-physiol-021909-135725. (Medline PMID: 20148682)

    Loreaux EL, Kaul B, Lorenz JN, Lingrel JB. Ouabain-Sensitive alpha1 Na,K-ATPase enhances natriuretic response to saline load. J Am Soc Nephrol. 2008 Oct;19(10):1947-54. doi: 10.1681/ASN.2008020174. Epub 2008 Jul 30. (Medline PMID: 18667729)

    Dostanic-Larson I, Van Huysse JW, Lorenz JN, Lingrel JB. The highly conserved cardiac glycoside binding site of Na,K-ATPase plays a role in blood pressure regulation. Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15845-50. doi: 10.1073/pnas.0507358102. Epub 2005 Oct 21. (Medline PMID: 16243970)

    Colony and Husbandry Information

    Colony Surveillance Program and Current Health Reports

    Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc_health@med.unc.edu.
    Coat Color
    Black
    Eye
    do not know
    MMRRC Breeding System
    Backcross
    Generation
    Bred at the Univ. of Cincinnati and back-crossed with C57B/6J since c. 2006-Sanger sequencing in 2022 confirmed that the model has retained the original mutations without modification
    Overall Breeding Performance
    Excellent
    Viability and Fertility: Female Male Comments
    Homozygotes are viable: Yes Yes
    Homozygotes are fertile: Yes Yes
    Heterozygotes are fertile: Yes Yes
    Age Reproductive Decline: 4 to 6 months Undetermined
    Average litter size
    7 to 9
    Recommended wean age
    3 Weeks
    Average Pups Weaned
    7 to 9

    Order Request Information

    Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

    Cryopreserved material may be available upon request, please inquire to mmrrc@med.unc.edu for more information.

    A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Geoffrey Pinski.

    Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

    A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Geoffrey Pinski

    Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

    Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
    MMRRC Item # Description Distribution Fee / Unit (US $)
    *Shipping & Handling not included*
    Units Notes
    069685-UNC-SPERM Cryo-preserved spermatozoa $520.00 / $863.00
    Non-Profit / For-Profit
    Aliquot Approximate quantity3
    069685-UNC-RESUS Litter recovered from cryo-archive $3,088.00 / $5,126.00
    Non-Profit / For-Profit
    Litter Recovered litter4; additional fees for any special requests.
    Cryopreserved material may be available upon request, please inquire to mmrrc@med.unc.edu for more information.

    1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

    2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

    3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

    4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

    To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.